Antimicrobial peptides (AMP) form the cornerstone of eukaryotic immunity and provide a first line of defense against breach of the skin and mucosal surfaces by micro-organisms. Examples of natural AMP include the defensin and cathelicidin families of peptides. These AMP are heterogeneous in length, sequence and structure, but common to most is their small size, net cationic charge and amphipathic structure. Small, cationic antimicrobial peptides have also been isolated from many bacteria, fungi, plants, invertebrates and vertebrates and would therefore appear also to play a role in prokaryotic defenses.
Natural AMP exhibit broad-spectrum activity against Gram-positive and Gram-negative bacteria, yeasts, fungi and enveloped viruses. Microbial pathogens do not seem to acquire resistance to these cationic peptides and as such, AMP have been conserved as a vital innate immune host defense molecules through millennia of evolution. It is not surprising therefore that AMP have been implicated as potential targets for therapeutics for a wide range of infections. However, the fact that they are technically challenging and costly to produce in recombinant systems and have potent chemotactic and inflammatory biological functions rules out natural AMP forms for use as therapeutics.
In our co-pending application we have shown that linear peptides rich in certain basic residues such as lysine or arginine possess antimicrobial activity, and, in particular, anti-fungal activity. There remains, however, a need for further agents that can be used in the treatment or prevention of microbial infections.